Description:

My current research interests are in understanding the role of dietary nutrients in the development of prostate cancer. In particular, I have been characterizing bioactivation of carcinogens in the prostate, a tissue with limited cytochrome P450 activity. I have identified a novel molecular target for nutrients in the prostate, which is a protein that oxidizes prostate carcinogens to DNA-reactive metabolites and generates cellular oxidative stress. Several important nutrients, in particular, ferulic acid, vanillic acid and epigallocatechin gallate, are effective and potent inhibitors of this enzyme and may suppress the stress response and this may be an important mechanism of their chemoreventative activity. I have been using a variety of different cell types including prostate tumor cells to characterize the process of oxidative stress. In these studies, which utilized self-referencing oxygen sensors, a major effort has focused on determining if oxygen utilization by individual cells and the cell monolayer, matches diffusion of oxygen from the surrounding environment. Studies were also initiated to determine if cells are able to recover from hypoxia, a major contributor to the oxidative stress response.

Progress:

In additional studies I have been characterizing cellular responses to paraquat, a redox active herbicide known to be toxic to the lung and kidney. Using self-referencing biosensors, he has determined that during reduction of paraquat, cells increase oxygen consumption, presumably due to regeneration of paraquat in cells in the presence of oxygen. These reactions were found to be independent of mitochondrial respiration and dependent on NADPH oxidase activity. Moreover, changes in cellular oxygen utilization were found to be directly correlated with expression of genes known to be redox active including cyclooxygenase-2 and heme oxygenase-1. These data indicate that changes in oxygen utilization in target cells in response to paraquat is likely to be critical in its mechanism of toxicity.